The proposed studies will investigate the hormonal regulation of arrest and reproductive states in female mosquitoes. Three peptide hormones are known or thought to control processes key to the maintenance of these states in the yellow fever mosquito, Aedes aegypti. 1) Ovary ecdysteroidogenic hormone I (OEH I) stimulates ovary steroidogenesis and yolk deposition in blood-fed decapitated females. Further studies of OEH I will define motifs required for bioactivity and lead to the identification of its receptor in ovaries. 2) Insulin-like peptides (ILP's) are ubiquitous in animals, and a yet to be identified mosquito ILP is thought to marshal nutrient stores in females in both the arrest and reproductive states, an action comparable to that of vertebrate insulin. A candidate insulin receptor has been identified in fat body and ovaries of females. An ILP and the insulin receptor may also regulate ovary steroidogenesis, as indicated by the action of bovine insulin. Isolation of an ILP from a three million head extract will lead to its structural and functional characterization and to a study of its binding to the insulin receptor. 3) A recently characterized neuropeptide F is related to the neuropeptide YIF family of peptides known to have a central role in the regulation of appetite and digestion in mammals and an invertebrate. The role of the mosquito NPF in the regulation of these processes in females will be ascertained by bioassays and the characterization of its receptor. As these studies progress, the degree to which these regulatory peptides are conserved in the malaria mosquito, Anopheles gambiae, will be determined. These studies will lead to a better understanding of how female mosquitoes are able to sustain the development of pathogens that vectored to humans and point to mechanisms that can be targeted for novel genetic or chemical controls of mosquito population.